Research in my laboratory focuses on studies of insulin action and
how insulin's action is altered by insulin resistance, obesity, and
diabetes mellitus. Specific studies currently underway involve
measurement of the action of insulin to regulate its own delivery to
skeletal muscle by acting on endothelial cells and smooth muscle cells.
Insulin relaxes smooth muscle cells associated with terminal arterioles
and dilates microvascular vessels to enhance tissue perfusion, thereby
increasing the delivery of both insulin and glucose to the tissues.
This vasodilator effect appears to be secondary to insulin's action on
the endothelial cell to increase the production of nitric oxide via the
activation of the enzyme nitric oxide synthase.

We have also demonstrated a second effect of insulin on the
endothelial cell. This involves insulin promoting its own uptake at the
luminal surface of the endothelial cell and which then transports the
insulin across to the ablumenal surface of the cell where it is
released and becomes available to act on target tissues like adipocytes
and myocytes. We have experimental evidence that both the ability of
insulin to cause smooth muscle relaxation and to promote its own
transport are impaired in states of insulin resistance (e.g. obesity,
type 2 diabetes). This step involving insulin transport across the
endothelium appears to be the rate limiting step for overall insulin
action on skeletal muscle (which is the major target tissue for
insulin-mediated glucose disposal).

We are also studying how these processes are affected by the action
of other growth factors (growth hormone and IGF-I). A major hypothesis
which we are exploring is that a significant fraction of the insulin
resistance which is encountered in skeletal muscle in states like
obesity, diabetes, and hypertension is attributable to impaired action
of insulin on the microvasculature in addition to any effect on the
muscle cell per se.